4. Location of Glutamate Receptors in the Thalamus

The advent of receptor cloning has allowed the production of selective antibodies for most of the known glutamate receptors, and many of these have been used to map the distribution of receptors in the thalamus, as well as in other parts of the nervous system, at both the light- and electron-microscopic level.

4.1 Neuronal elements

mRNA expression for the AMPA receptors is generally low in the thalamus, although not absent (Keinaenen et al., 1990; Petralia & Wenthold, 1992; Sato et al., 1993; Sommer et al., 1990). Immunostaining for GluR1 indicates that the relay nuclei and nrt are virtually unlabelled, although there is label in medial thalamic nuclei. In contrast, there is diffuse immunostaining for GluR2/3 throughout the thalamus (Kharazia et al., 1995; Martin et al., 1993; Spreafico et al., 1994). In the nrt, there is very intense staining for GluR4 (Kharazia et al., 1995; Martin et al., 1993; Page & Everitt, 1995; Spreafico et al., 1994). It is noteworthy that all of these receptors are found in dendrites and somata, with little evidence for a presynaptic localisation. Less is known about the location of kainate receptors, but KA2 and GluR6/7 immunoreactive staining have been detected in the thalamic relay nuclei and nrt, the latter area having somewhat denser staining (Petralia et al., 1994a). Expression of GluR7 is in excess of other kainate receptors in nrt, and thus it is conceivable that this region may have predominantly homomeric GluR7 rather than other kainate receptor types (Wisden & Seeburg, 1993). This is intriguing given the apparent lack of agonist responses of this subunit composition (see section 3.1), however, there is evidence to suggest that GluR7 is present along with KA2 in postsynaptic densities in some brain areas (Petralia et al., 1994a).

In situ hybridization studies reveal that NR1 and NR2A, NR2B are expressed in the thalamus. NR2C is not expressed in this brain area, and NR2D is located in the medial thalamus rather than in the thalamic relay nuclei (Buller et al., 1994; Monyer et al., 1994; Watanabe et al., 1993). Immunohistochemistry using antibody to NR1 indicates that this subunit is widely distributed throughout the brain, including the thalamus (Petralia et al., 1994c), thus indicating the presence of functional NMDA receptors. A similar approach using NR1 antibodies indicates that NMDA receptors are located not only on dendrites of thalamic relay neurones and nrt cells, but also on presynaptic terminals within the rat VB (Kharazia et al., 1995). Whether these presynaptic NR1 subunits are part of functional NMDA receptors remains to be elucidated.

The thalamus is one of the areas of the brain which shows highest expression of mGluR1 mRNA (section 3.3). There is also substantial mGluR5 expression, but very little mGluR2 mRNA (Ohishi et al., 1993a). Ultrastructural analysis with antibodies raised to mGluR1a indicate that this receptor is located on dendrites of thalamic relay cells and nrt neurones (Martin et al., 1992). It seems to be the case that there is no mGluR1 located on presynaptic elements (Martin et al., 1992; Romano et al., 1995). Light-microscopy with mGluR5 antibody has shown that this too is located in the neuropil of the thalamic relay nuclei and nrt (Romano et al., 1995). Interestingly, there is evidence that this receptor may be presynaptic in some brain areas (Romano et al., 1995), and this may also be the case in the thalamus (Godwin et al., 1995). There is less information available concerning the localisation of other mGluRs in the thalamus, although mRNAs for mGluR3, mGluR4 and mGluR7 are expressed (see section 3.3). More detailed analysis will depend on the use of specific antibodies for these receptors. However, given the high expression of mGluR3 mRNA in nrt (Catania et al., 1994; Ohishi et al., 1993b; Tanabe et al., 1993), and that this receptor may be involved in certain presynaptic responses in the thalamus (Salt & Eaton 1995a), it has been suggested that mGluR3 is located on terminals of GABAergic nrt neurones projecting into the thalamic relay nuclei (Salt & Eaton, 1995a). Preliminary electron microscopical data from the cat LGN would support this hypothesis (Van Horn et al., 1995).

Recently, studies have been carried out to elucidate the synaptic localisations of glutamate receptors in the thalamus, and these have shown that virtually all rat VB relay neurones are immunopositive for NR1, GluR2 and mGluR1a, all of these being located on postsynaptic dendrites. Interestingly, mGluR1a is found at the periphery of synapses (Kharazia et al., 1995), in a similar manner to that described in the cerebellum and hippocampus (Nusser et al., 1994). Furthermore, it has been shown that both NR1 and mGluR1a are postsynaptic to cortico-fugal fibres terminating on VB thalamic relay neurones (Kharazia et al., 1995). Preliminary evidence from the cat LGN suggests that mGluR1a is postsynaptic to cortical terminals on GABAergic dendrites (Godwin et al., 1995), although this does not preclude a localisation on other cellular elements.

4.2 Glial elements

Both GluR1 and GluR4 immunoreactivity have been seen on thalamic astrocytes (Kharazia et al., 1995). In contrast, it appears that these cells do not stain for NR1 (Kharazia et al., 1995), and there is no clear evidence of staining for NR2A/B in glia (Petralia et al., 1994b). A number of mGluRs have been localised on astrocytes and many astrocytic preparations respond with metabotropic responses to excitatory amino acid agonists (Chiu & Kriegler, 1994; Prezeau et al., 1994), but it is unclear what the situation is in the thalamus. Nevertheless, given that there is strong evidence for glial localisation of mGluR3 from other brain areas (Ohishi et al., 1993b; Testa et al., 1994), and that there is substantial mGluR3 mRNA in the thalamus and particularly in nrt (Catania et al., 1994; Ohishi et al., 1993b; Tanabe et al., 1993), it seems reasonable to predict that thalamic glia possess mGluR3, if not other receptors. Preliminary data with an antibody to mGluR2/3 would support the notion that mGluR3 is located on thalamic astrocytes (Jeffery et al., 1996).

Please note: this document is part of the HTML version of a paper originally published in print in Progress in Neurobiology.

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